Fig. 43.10 ). Cortisol enhances gene expression of the key hepatic gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK). Cortisol also decreases GLUT4-mediated glucose uptake in skeletal muscle and adipose tissue. During the interdigestive period (low insulin-glucagon ratio), cortisol promotes glucose sparing by potentiating the effects of catecholamines on lipolysis, thereby making FFAs available as energy sources. Cortisol inhibits protein synthesis and increases proteolysis, especially in skeletal muscle, thereby providing a rich source of carbon for hepatic gluconeogenesis.
Fig. 43.10 also contrasts the normal role of cortisol in response to stress and the effects of chronically elevated cortisol as a result of pathological conditions. As discussed later, there are important differences in the overall metabolic effects of cortisol between these two states, particularly with respect to lipid metabolism. During stress, cortisol synergizes with catecholamines and glucagon to promote a lipolytic, gluconeogenic, ketogenic, and glycogenolytic metabolic response while synergizing with catecholamines to promote an appropriate cardiovascular response. During chronically elevated cortisol secondary to pathological overproduction, cortisol synergizes with insulin in the context of elevated levels of glucose (from increased appetite) and hyperinsulinemia (from elevated glucose and glucose intolerance) to promote lipogenesis and truncal (abdominal/ visceral) adiposity.
Cortisol reinforces its effects on blood glucose by its positive effects on the cardiovascular system. Cortisol has permissive actions on catecholamines by increasing adrenergic receptor expression and thereby contributes to cardiac output and blood pressure. Cortisol stimulates erythropoietin synthesis and hence increases red blood cell production. Anemia occurs when cortisol is deficient, and polycythemia occurs when cortisol levels are excessive.
Inflammation and immune responses are often part of the response to stress. However, inflammation and immune responses have the potential for significant harm and may cause death if they are not held in homeostatic balance. As a stress hormone, cortisol plays an important role in maintaining immune homeostasis. Cortisol, along with epinephrine and norepinephrine, represses production of proinflammatory cytokines and stimulates production of antiinflammatory cytokines.
Stress during interdigestive period (e.g., elderly person slips on ice and dislocates hip) Liver ˜ Glycogenolysis ˜ Gluconeogenesis
Metabolic responses to stress ensure sufficient energy to meet increased demand on body, and will maintain adequate blood glucose levels necessary for conscious, deliberate action by the individual. The metabolic responses are supported by cardiovascular ones, first by those induced by the sympathoadrenal output (see Fig.
43.6) but also by cortisol, which optimizes adrenergic receptor function. Cortisol will also contribute to providing energy for the incipient inflammatory and immune response to this stress, but will also protect the individual from the potential damage of unregulated inflammation.